Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus

Simon H. Jiang (), Vicki Athanasopoulos, Julia I. Ellyard, Aaron Chuah, Jean Cappello, Amelia Cook, Savit B. Prabhu, Jacob Cardenas, Jinghua Gu, Maurice Stanley, Jonathan A. Roco, Ilenia Papa, Mehmet Yabas, Giles D. Walters, Gaetan Burgio, Kathryn McKeon, James M. Byers, Charlotte Burrin, Anselm Enders, Lisa A. Miosge, Pablo F. Canete, Marija Jelusic, Velibor Tasic, Adrian C. Lungu, Stephen I. Alexander, Arthur R. Kitching, David A. Fulcher, Nan Shen, Todor Arsov, Paul A. Gatenby, Jeff J. Babon, Dominic F. Mallon, Carmen Lucas Collantes, Eric A. Stone, Philip Wu, Matthew A. Field, Thomas D. Andrews, Eun Cho, Virginia Pascual, Matthew C. Cook and Carola G. Vinuesa ()
Additional contact information
Simon H. Jiang: John Curtin School of Medical Research
Vicki Athanasopoulos: John Curtin School of Medical Research
Julia I. Ellyard: John Curtin School of Medical Research
Aaron Chuah: NHMRC Centre for Research Excellence
Jean Cappello: John Curtin School of Medical Research
Amelia Cook: John Curtin School of Medical Research
Savit B. Prabhu: John Curtin School of Medical Research
Jacob Cardenas: Baylor Medical Institute
Jinghua Gu: Baylor Medical Institute
Maurice Stanley: John Curtin School of Medical Research
Jonathan A. Roco: John Curtin School of Medical Research
Ilenia Papa: John Curtin School of Medical Research
Mehmet Yabas: John Curtin School of Medical Research
Giles D. Walters: John Curtin School of Medical Research
Gaetan Burgio: John Curtin School of Medical Research
Kathryn McKeon: John Curtin School of Medical Research
James M. Byers: John Curtin School of Medical Research
Charlotte Burrin: John Curtin School of Medical Research
Anselm Enders: John Curtin School of Medical Research
Lisa A. Miosge: John Curtin School of Medical Research
Pablo F. Canete: John Curtin School of Medical Research
Marija Jelusic: University of Zagreb School of Medicine
Velibor Tasic: University Children’s Hospital, Medical School
Adrian C. Lungu: Department of Pediatric Nephrology, Fundeni Clinical Institute
Stephen I. Alexander: NHMRC Centre for Research Excellence
Arthur R. Kitching: NHMRC Centre for Research Excellence
David A. Fulcher: John Curtin School of Medical Research
Nan Shen: JiaoTong University Shanghai
Todor Arsov: John Curtin School of Medical Research
Paul A. Gatenby: The Canberra Hospital
Jeff J. Babon: Walter and Eliza Hall Institute
Dominic F. Mallon: Immunology PathWest Fiona Stanley Hospital
Carmen Lucas Collantes: Children’s University Hospital Niño Jesús
Eric A. Stone: Research School of Biology and Research School of Finance, Actuarial Studies and Statistics
Philip Wu: NHMRC Centre for Research Excellence
Matthew A. Field: NHMRC Centre for Research Excellence
Thomas D. Andrews: NHMRC Centre for Research Excellence
Eun Cho: NHMRC Centre for Research Excellence
Virginia Pascual: Baylor Medical Institute
Matthew C. Cook: John Curtin School of Medical Research
Carola G. Vinuesa: John Curtin School of Medical Research

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-10242-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10242-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-10242-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().